Mosquito-borne diseases present an increasing global human health threat. These diseases reflect a significant resurgence in most developing countries, and also are emerging as clear threats for epidemic outbreaks in developed countries. Many factors contribute to the inability to date to prevent or control these diseases including poor progress in vaccine development, emergence of insecticide resistance in mosquito populations, drug resistance among parasite populations, lack of support in many developing countries for mosquito control programs, and increased global travel. This proposal seeks to initiate investigations on the autogeny trait observed in many mosquito species examined to date;autogenous females are able to produce an egg batch without the typical need for a blood meal as is typical with most female mosquitoes. Understanding the fundamental biology of mosquito populations, and particularly aspects of vitellogenesis, is critical to proposed efforts to utilize novel genetic approaches for controlling mosquito-borne diseases. At present, no knowledge exists on the molecular determinants of autogeny in any mosquito species. The focus of this proposal is the detailed genetic investigation of autogeny in Aedes aegypti as the model mosquito species for rapidly and efficiently uncovering the genetic basis for autogeny. Our long-term goals for these efforts are to eventually uncover genetic mechanisms likely common to autogeny determination in most if not all mosquito species. Aedes aegypti is the primary global vector for dengue virus. Dengue is a threat to >2.5 billion people, with an annual incidence of ~50 million cases and ~500,000 cases of DHF/DSS resulting in ~24,000 deaths per year. The objectives of this proposal are based on the general hypothesis that genes associated with the autogeny phenotype can be identified and isolated by positional cloning techniques. The proposed research will define a strong foundation toward the eventual detailed investigations of the genes determining autogeny and the knowledge obtained from the detailed understanding of the associated biochemical pathways will increase our basic understanding of vitellogenesis in mosquitoes which has implications for predicting vectorial capacity among mosquito populations. This could have several potential applications including transgene constructs that promote altered and disease limiting behaviors that significantly reduce vectorial capacity, development of targeted biopesticides, or identification of biologically relevant antagonists that disrupt behaviors critical to pathogen transmission or survival. The research plan builds upon and enhances the information obtained from the Ae. aegypti genome project to develop the necessary tools toward the eventual complete elucidation of these gene relationships and their phenotypic outcome. The specific aims of the project are to: 1) perform fine-scale genetic mapping to identify regions containing genes that determine the autogeny phenotype in Aedes aegypti and 2) conduct high-resolution, fine-scale physical mapping of an Aedes aegypti BAC library. PUBLIC HEALTH RELEVANCE: Aedes aegypti is the primary vector for dengue virus. No vaccines are available and disease prevention is largely dependent on avoiding contact with infected mosquitoes. The proposed research will provide valuable new information on the biology of this mosquito relating to the ability of some females to produce eggs without obtaining a blood meal.